Tailorable surface topology for antifouling coatings

ABSTRACT

Embodiments are directed to a method of making an antifouling and bactericidal coating with tailorable surface topology. The method includes depositing a layer of branched polyethyleneimine (BPEI) and diamino-functionalized poly(propylene oxide) (PPO) in a mixture of water and organic solvent on a substrate to form a layer of BPEI/PPO. The method includes depositing a layer of glyoxal in a water-containing solution on the layer of BPEI/PPO. The method further includes curing the layer of BPEI/PPO and layer of glyoxal to form a homogenous, glyoxal crosslinked BPEI/PPO coating, where the curing induces local precipitation and alteration of the glyoxal crosslinked BPEI/PPO coating to provide a textured surface.

BACKGROUND

The present invention relates in general to antifouling coatings. Morespecifically, the present invention relates to a tailorable surfacetopology for antifouling coatings.

The accumulation of microorganisms on wetted surfaces, or biofouling, isa ubiquitous problem for materials in a broad range of applications,such as medical devices, marine instruments, food processing, and evendomestic drains. Generally, bacteria initiate biofouling by formingbiofilms, which include highly ordered adherent colonies, commonlywithin a self-produced matrix of extracellular polymeric substance.

In the medical field, infection is a potential complication of implantedmedical devices. Bacterial colonization and subsequent biofilm formationare difficult to diagnose and treat. Biofilms are a primary cause ofpersistent infections because of their resistance to antibiotics,potential release of harmful toxins, and ability to spreadmicroorganisms. Biofilms can also cause implantable devices tomalfunction.

Often, extreme measures, such as removal of the infected device from thepatient's body, are the only viable management option. Althoughdisinfection techniques and prophylactic antibiotic treatment are usedto prevent colonization during procedures, such practices are notcompletely effective in preventing perioperative bacterial colonization.Moreover, the risk of bacterial colonization on, for example, aprosthetic joint can be present even long after it has been implanted.The use of implantable devices, such as prosthetic joints, heart valves,artificial hearts, vascular stents and grafts, cardiac pacemakers anddefibrillators, nerve stimulation devices, gastric pacers, vascularcatheters and ports (e.g., Port-A-Cath)) is growing, and therefore, thenumber of immunocompromised patients resulting from advancedtherapeutics is also growing.

For a variety of reasons, antibiotic treatments to eliminatecolonization and infection associated with implantable substances anddevices can be limited in their ability to eradicate bacteria and fungiinvolved in the above processes. For example, antibiotic concentrationscan be reduced deep inside the biofilm due to limited diffusion.Antibiotics also may be unable to generally eliminate “the last”pathogen cells, which is typically accomplished by the immune systemthat also may not optimally function in the presence of implantabledevices. Microorganisms also possess the ability to persist, i.e., tobecome metabolically inactive and thus functionally relatively resistantto antibiotics. The pandemic of antibiotic resistance makes treatingdevice-associated infections even more challenging. In fact, antibioticresistance is frequently encountered with microorganisms that causedevice-associated infections (e.g., Enterococci and Staphylococci).Therefore, there is a clear need for means and methods to prevent theformation of biofilms on implantable devices.

Consequently, considerable efforts were dedicated, in recent years, todeveloping antibacterial surfaces. Such surfaces can be classified intotwo categories: (i) antifouling surfaces that prevent the adhesion ofmicroorganisms, and (ii) bactericidal surfaces that trigger bacteriakilling.

Typical strategies for the design of antibacterial surfaces involveeither supramolecular (non-covalent) coating of the surface ormodification of the surface (i.e chemical modification or structuring).Antifouling properties are commonly obtained by the incorporation of,for example, oligo or poly(ethylene glycol) (PEG) to increasehydrophilicity and resist bacteria attachment. Bactericidalcharacteristics, on the other hand, may be obtained by functionalizationwith releasable bacteria-killing substances, such as silvernanoparticles (Ag NPs) and antibiotics, or decoration withcontact-killing bactericidal moieties like quaternary ammonium salts.Current technologies, however, suffer several shortcomings including,just to name a few, long-term antibacterial performances and stability,development of bacterial resistance, and scalability to an industrialsetting. While bacterial cell lysis on biocide-functionalized surfacesreduces the rate of biofilm formation, recent reports evidenced that acombination of both antifouling and bactericidal properties wasnecessary to insure long-term efficacy of the surfaces.

An environmentally friendly and easy to process method for protectingsurfaces and devices for prolonged periods of time using anantimicrobial/antifouling strategy to prevent biofilm formation remainsa technologic and scientific challenge.

SUMMARY

Embodiments of the present invention are directed to a method of makingan antifouling and bactericidal coating with tailorable surfacetopology. The method includes depositing a layer of branchedpolyethyleneimine (BPEI) and diamino-functionalized poly(propyleneoxide) (PPO) in a mixture of water and organic solvent on a substrate toform a layer of BPEI/PPO. The method includes depositing a layer ofglyoxal in a water-containing solution on the layer of BPEI/PPO. Themethod further includes curing the layer of BPEI/PPO and layer ofglyoxal to form a homogenous, glyoxal crosslinked BPEI/PPO coating,where the curing induces local precipitation and alteration of a surfacetopology of the glyoxal crosslinked BPEI/PPO coating to provide atextured surface. Advantages of the textured surface include providingan antifouling and bactericidal coating.

According to one or more embodiments, a method of making an antifoulingcoating with tailorable surface topology includes providing a mold witha pattern of indentions and protrusions. The method includes forming alayer of fluorinated polythioaminal on the pattern of indentions andprotrusions of the mold. The method further includes heating the layerof fluorinated polythioaminal to induce crosslinking and transfer thepattern into the layer of fluorinated polythioaminal. The method furtherincludes removing the mold from the layer of fluorinated polythioaminal,the layer of fluorinated polythioaminal including a negative pattern ofthe mold. Advantages of the method include being able to easily form asurface with a highly fluorinated antifouling network that is based on anegative pattern of the mold.

According to one or more embodiments, a method of making an antifoulingcoating with a textured surface includes forming a fluorinatedpolythioether by a nucleophilic aromatic substitution reaction. Themethod further includes curing the polythioether to provide a film thatis semi-crystalline or crystalline. Advantages of the method include theability to rapidly develop a broad array of new hydrophobic materials.

Additional technical features and benefits are realized through thetechniques of the present invention. Embodiments and aspects of theinvention are described in detail herein and are considered a part ofthe claimed subject matter. For a better understanding, refer to thedetailed description and to the drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

The specifics of the exclusive rights described herein are particularlypointed out and distinctly claimed in the claims at the conclusion ofthe specification. The foregoing and other features and advantages ofthe embodiments of the invention are apparent from the followingdetailed description taken in conjunction with the accompanying drawingsin which:

FIG. 1 depicts methods for forming a coating according to embodiments ofthe invention;

FIG. 2A depicts an antifouling property of a coating according toembodiments of the invention;

FIG. 2B depicts a bactericidal property of a coating according toembodiments of the invention;

FIG. 3 depicts a profilometer trace of a coating prepared in accordancewith embodiments of the invention;

FIG. 4A depicts antifouling activity of a material formed according toembodiments of the invention;

FIG. 4B depicts antifouling activity of a material formed according toembodiments of the invention;

FIG. 4C depicts live/dead assays of a material formed according toembodiments of the invention;

FIG. 5A depicts a reaction scheme for forming polymers according toembodiments of the invention;

FIG. 5B depicts a gel permeation chromatography (GPC) trace of amaterial formed to embodiments of the invention;

FIG. 6A depicts a method for forming a material according to embodimentsof the invention;

FIG. 6B depicts a method for forming a material according to embodimentsof the invention;

FIG. 6C depicts a method for forming a material according to embodimentsof the invention;

FIG. 7 depicts a method for measuring a contact angle of a materialforming according to embodiments of the invention; and

FIG. 8 depicts a graph of storage modulus as a function of temperaturefor a material formed according to embodiments of the invention.

The diagrams depicted herein are illustrative. There can be manyvariations to the diagram or the operations described therein withoutdeparting from the spirit of the invention. For instance, the actionscan be performed in a differing order or actions can be added, deletedor modified. Also, the term “coupled” and variations thereof describeshaving a communications path between two elements and does not imply adirect connection between the elements with no interveningelements/connections between them. All of these variations areconsidered a part of the specification.

In the accompanying figures and following detailed description of thedisclosed embodiments, the various elements illustrated in the figuresare provided with two or three digit reference numbers. With minorexceptions, the leftmost digit(s) of each reference number correspond tothe figure in which its element is first illustrated.

DETAILED DESCRIPTION

Turning now to an overview of technologies that are more specificallyrelevant to aspects of the invention, embodiments of the inventionrelate to systems and methods for preventing and/or treating bacterialcolonization, biofilm formation, or infection involving an implantablemedical device. Current technologies, as mentioned above, suffer severalshortcomings, including long-term antibacterial performance andstability, development of bacterial resistance, and scalability to anindustrial setting. Furthermore, while bacterial cell lysis onbiocide-functionalized surfaces reduces the rate of biofilm formation,recent reports evidenced that a combination of both antifouling andbactericidal properties was necessary to insure long-term efficacy ofthe surfaces.

Turning now to an overview of the aspects of the invention, embodimentsof the invention address the above-described shortcomings of the priorart by providing an antimicrobial/antifouling coating that is obtainedby texturing the surface (or altering the surface topology) of animplantable medical device either prior or post-polymerization/curing.Various embodiments include surface texturing of a crosslinkedpolyethyleneimine (PEI)-glyoxal coating obtained by layer-by-layer spraycoating, surface texturing of a hydrophobic (fluorinated) thioaminalnetwork obtained by nano-imprinting while curing, and surface texturingof a hydrophobic (fluorinated) thermoplastic material induced bycrystallization, post or during synthesis. These methods offer atechnology platform to more diverse, versatile, economical andlarge-scale applications for antimicrobial materials.

Implantable medical devices to which a coating (film or layer) of thepresent invention can be applied include, but are not limited to, aprosthetic joint, a vascular line, stent or graft, a venous filter, atooth implant, a cochlear implant, a metal used for bone fractureinternal fixation, a urinary catheter, a ventriculoperitoneal shunt, acardiac or nerve pacemaker, a heart valve, or a ventricular assistdevice.

The above-described aspects of the invention address the shortcomings ofthe prior art by offering a technology platform to more diverse,versatile, economical and large-scale applications for antimicrobialmaterials.

Turning now to a more detailed description of aspects of the presentinvention, FIG. 1 depicts methods for forming a homogenous coatingaccording to embodiments of the invention. Surface texturing induced bymicro-precipitation or nano-precipitation in the solvent mixture is usedfor curing a crosslinked coating, which is described in further detailbelow.

Poly(ethylene imine) (PEI) is an antimicrobial that kills bacteria in acontact-killing faction (i.e., without release of toxic moieties fromthe surface). PEI has amines (tertiary, secondary, and primary)available for attachment of functional groups. However, when used as acoating, PEI may not exhibit long-term efficacy, like otherantimicrobial materials. PEI nanoparticles, crosslinked by reductiveamination or nucleophilic substitution, are efficient antimicrobialagents. Conventional methods for incorporating PEI antimicrobialmaterials, however, include multistep-modification procedures, rely onharsh, environmentally unfriendly processing, and/or lack a scalabledeposition method applicable to an industrial setting. Furthermore, whenused as a coating, PEI suffers, like many antimicrobial materials, frompoor long-term efficacy.

Therefore, according to one or more embodiments, branched PEI (BPEI) andamino-functionalized poly(propylene oxide) (PPO) are crosslinked at thesurface of a substrate using its available primary amines, which arereacted with glyoxal. The reaction of primary amines with glyoxal canlead to a mixture of products (α-hydroxy amine (1), imine (2), and 4/1adducts (3)) as depicted in Scheme 1 below.

The occurrence of each product depends on the nature of the amine,stoichiometry, solvent and temperature. In model studies performed atroom temperature and analyzed by nuclear magnetic resonance spectroscopy(NMR), the major product observed is the bis-imine product (2). However,traces of another product attributed to the presence of product (3) wereobserved while varying the stoichiometry. As the coating is cured atelevated temperature after deposition, to remove the solvent and allowfor maximum crosslinking density, the ratio of product (2) to product(3) should decrease in the final material.

In some embodiments, BPEI, PPO, and glyoxal are deposited fromwater-containing solutions. Advantageously, this approach allows for amore environment-friendly process. Most interestingly, the reaction ofBPEI with glyoxal is very fast and leads to an immediate gelation of thereaction medium when mixing aqueous solutions of BPEI at a concentrationof greater than about 25 weight percent and glyoxal at a concentrationof greater than about 5 weight percent. Taking advantage of this fastgelation, a layer-by-layer process can be achieved.

FIG. 1 illustrates a cross-sectional view of a structure having a firstBPEI/PPO layer 102 formed on a substrate 101. The first BPEI/PPO layer102 is viscous enough to allow for good coverage of the substrate 101surface. A first glyoxal layer 103 is formed on a surface of the firstBPEI/PPO layer 102. The first BPEI/PPO layer 102 and the first glyoxallayer 103 can be formed or deposited over the substrate 101 using anysuitable process, such as, for example, deposition by dip-coating orspray-coating.

According to one or more embodiments, the first BPEI/PPO layer 102 andfirst glyoxal layer 103 are successively sprayed onto the substrate 101(e.g., APTES-functionalized glass substrate) from nozzles positionedover the substrate 101 at a distance of about 15 centimeters at apressure of about 25 psi.

Additional alternating layers of BPEI, BPEI/PPO, and glyoxal can beformed on the substrate 101 in a similar manner. The total number ofdeposited layers is chosen depending on the desired thickness of thefinal coating. One or more additional layer of each of BPEI, BPEI/PPO,or glyoxal can be deposited before curing. In some embodiments, thestructure is formed from a single layer of BPEI/PPO and glyoxal (2 totallayers). In other embodiments, four (4) or nine (9) layers are used,although other thicknesses (and consequently, total number of layers)are within the contemplated scope of the invention. In some embodiments,depending on the concentration of the BPEI/PPO layers, the concentrationof the glyoxal layers, and the temperature (e.g., for solutions havinggreater than about 25 wt % BPEI and 5 wt % glyoxal at a temperature ofabout 20 degrees Celsius), immediate gelation is observed.

After depositing the layers of BPEI, BPEI/PPO, and glyoxal, the coatingis cured 111 to remove water (and/or solvent) and form a homogenouscoating 104 with BPEI-glyoxal crosslinks 105. In some embodiments, thefirst BPEI layer 102 and the first glyoxal layer 103 are cured at atemperature of about 30 degrees Celsius for about 1 hour. In someembodiments, the first BPEI layer 102 and the first glyoxal layer 103are cured at a gradually increasing temperature of about 30 to about 120degrees Celsius over about 1 hour. In some embodiments, the first BPEIlayer 102 and the first glyoxal layer 103 are cured at a temperature ofabout 120 degrees Celsius for about 1 hour. In some embodiments, athree-stage thermal treatment is used to cure: (1) a first stage cure ata temperature of 30 degrees Celsius for 1 hour; (2) a second stage cureat a gradually rising temperature of about 30 degrees Celsius to about120 degrees Celsius over 1 hour; and (3) a third stage cure at atemperature of about 120 degrees Celsius for 1 hour. After curing, thesubstrate 101 is then allowed to cool down to room temperature.

The adhesion of the first BPEI or BPEI/PPO layer on the substrate 101can be promoted either by modification of the substrate 101 or by theaddition of adhesion promoter moieties. For example, the substrate 101can be functionalized with —NH₂ moieties by condensing3-aminopropyl)triethoxysilane (APTES) at the surface of the substrate101. The amine moieties attached at the surface of the substrate 101could then react with glyoxal during crosslinking. Alternatively,catechol-containing moieties can be added to the BPEI/glyoxal mixture topromote the adhesion of the crosslinked PEI/glyoxal polymer (homogenouslayer 104) to the substrate 101.

The positively charged amines (quaternary amines) of BPEI (in aqueoussolution) make the glyoxal-crosslinked BPEI coatings bactericidal. Asdepicted in FIGS. 2A and 2B, the antimicrobial properties of the coatingis enhanced by nano- or micro-patterning (nano- or micro-precipitation)using selective solvents, during curing, which is described in furtherdetail below.

To form a nano-pattern of micro-pattern, the layers forming the coating(BPEI, BPEI/PPO, and glyoxal) are deposited in solvents and mixtures ofsolvents that leads to phase-separation during later curing. Thephase-separation during curing forms a nano-pattern or a micro-patternof the coating on the surface of the substrate. The nanoscale andmicroscale patterns are due to local precipitation, wrinkling, oralteration of the surface topology. According to embodiments, curinginduces local precipitation and alteration of a surface topology of thehomogenous, glyoxal crosslinked BPEI coating to provide a texturedsurface.

As shown in FIG. 2A, the nano-patterned or micro-patterned coating 201functions as an antifouling surface, which prevents bacteria 202 fromadhering to the surface. The rough, irregular surface prevents bacteriafrom attaching. As shown in FIG. 2B, the coating 201 also functions as abactericidal coating that repels bacteria. Because the polymers in thecoating 201 can be positively charged by quaternization in aqueousmedia, they also kill bacteria on contact. When healthy bacteria 203come into contact with the cationic coating 201, the coating kills thebacteria (resulting in dead bacteria 204).

In an exemplary embodiment, successive depositions of a solution of PEIand diamino-functionalized poly(propylene oxide) (PPO) in isopropanoland a solution of glyoxal in a mixture of isopropanol and water is usedto phase separate the coating during curing. The PPO is included in thePEI solution to increase hydrophobicity and function as aphase-separator that alters the surface topology.

According to embodiments, the layers of BPEI, BPEI/PPO, and glyoxal aredeposited in organic solvents and aqueous mixtures to induceprecipitation upon curing. In an exemplary embodiment, a layer of BPEIin an organic solvent (e.g., isopropanol) is deposited, followed by alayer of glyoxal in organic solvent (e.g., isopropanol) and water. Localprecipitation occurs during curing to alter the surface topology of theresulting coating.

According to other embodiments, surface texturing is induced bynano-imprinting of a hydrophobic material. The hydrophobic material is afluorinated polythioaminal that is formed from the in-situ generation ofa reactive amine intermediate. According to some embodiments, thepolythioaminal is formed by reacting fluorinated dianilines anddithiols, in equimolar ratios, with paraformaldehyde. In-situ generationof a reactive intermediate imine further condenses with a dithiolmolecule to form the fluorinated polythioaminal.

FIG. 5A depicts a reaction scheme for forming a polythioaminal accordingto an exemplary embodiment. 4,4′-hexafluoroisopropylidene)dianiline and1,6-hexanedithiol are reacted with an excess of paraformaldehyde. Areactive imine intermediate condenses with a dithiol to form afluorinated polythioaminal.

At low temperatures, only linear polythioaminals are produced, but asthe temperature is increased, the multiple substitutions occur at thenitrogen positions to form a cross-linked network. These propertiesallow the polythioaminals to be textured on a substrate using imprintlithography (or nanoimprint lithography). A linear polymer is depositedonto a substrate, and then heated to form the permanent network thattakes the shape of substrate.

As mentioned above, the polythioaminals can be textured on a substrateusing nanoimprint lithography, which is a method of fabricatingnanometer scale patterns. Generally, nanoimprint lithography createspatterns by mechanical deformation of imprint resist and subsequentprocesses. Generally, the imprint resist is a polymer formulation thatis cured by heat or ultraviolet light during the imprinting. Adhesionbetween the resist and the template is controlled to allow properrelease.

FIG. 6A depicts a method for forming a nanoscale pattern of apolythioaminal coating according to embodiments. A mold 611 having apattern of a plurality of protrusions 620 and indentions 621 is providedand disposed onto a layer of polythioaminal 610 arranged on a substrate630. The polythioaminal 610 is heated, and the mold 611 is removed totransfer the pattern to the layer of polythioaminal, which then includesa plurality of protrusions 641 and indentions 640 that mirror thepattern of the mold 611 (a negative pattern of the mold). Themolded/texturized layer of polythioaminal 610 after heating includescrosslinks that forms a three-dimensional network.

FIG. 6B depicts a method for forming a nanoscale pattern of apolythioaminal coating according to embodiments. A mold 611 having apattern of a plurality of protrusions 620 and indentions 621 isprovided. A layer of polythioaminal 610 is disposed directly on the mold611. The layer of polythioaminal 610 is heated, and the mold 611 isremoved to transfer the pattern to the layer of polythioaminal, whichthen includes a plurality of protrusions 641 and indentions 640 thatmirror the pattern of the mold 611 (negative pattern). Themolded/texturized layer of polythioaminal 610 after heating includescrosslinks that forms a three-dimensional network.

FIG. 6C depicts a method for forming spin-coated polythioaminals andsubsequent network formation according to one or more embodiments. Athin layer of the polythioaminal polymer 610 (the imprint resist) isspin-coated onto the sample substrate 630. Then the mold 611, which haspredefined topological patterns, is brought into contact with thesubstrate having the polymer 610 disposed thereon. The mold 611 and thesubstrate 630 with the polymer 610 are pressed together under certainpressure. The polymer 610 is heated to a temperature above the glasstransition temperature, and the pattern on the mold 611 is pressed intothe softened polymer film, forming a crosslinked network that takes theshape of the mold 611. After being cooled down, the mold 611 isseparated from the sample and the pattern resist is left on thesubstrate 630 in the polymer network 604.

The polythioaminals are linear before heating. According to one or moreembodiments, the polydispersity index (PDI) of a polythioaminal is about2 when formed at a temperature in a range from about 25 to about 100° C.After increasing the temperature to about 100 to about 200° C., thelinear polymer undergoes multiple substitutions at the nitrogen group toform a cross-linked network, increasing the PDI.

These polythioaminal polymer networks can be generated with a variety ofnumber of electron deficient diamines. According to one or moreembodiments, the polythioaminal is formed from reacting substituted orunsubstituted dianiline with a dithiol in the presence of an aldehyde,for example, paraformaldehyde or formaldehyde.

As the fluorine content increases, the contact angle of the polymernetwork with the substrate increases. According to one or moreembodiments, the contact angle of the polymer network increases to above100° . Thus, these materials are easy to process, hydrophobic coatings.

According to one or more embodiments, surface texturing of a medicaldevice surface is induced by crystallization of a coating, which isdescribed in further detail below.

The development of new, implantable devices for health monitoring hasthe potential to revolutionize personalized medicine and diseasediagnosis. However, as with many implantable materials, it is essentialthat they are biocompatible, particularly with regard to preventingbacterial infection and biofilm formation. To this end, highlyhydrophobic surfaces have the potential to prevent bacterial adhesionand the formation of biofilms. One approach to generate hydrophobicsurfaces is to coat the device with an appropriate polymeric materialthat is itself highly hydrophobic in nature. Such materials includepolymers with high fluorine content or long alkyl chains, both of whichcan impart hydrophobic properties to materials.

As described herein, fluorinated polythioethers are formed via anucleophilic aromatic substitution reaction (SN_(Ar)). The fluorinatedpolythioethers are highly hydrophobic materials that prevent bacterialadhesion and formation of biofilms.

According to one or more embodiments, the surfaces of the fluorinatedpolythioether materials (films or coatings) are also texturized andinclude surface topology such that the microbes cannot adhere and formbiofilms. The texturized surfaces thus provide distinctive antifoulingsurfaces. The texture results from being semi-crystalline or crystallinein nature.

One method to achieve surface topology in an easy, facile andnon-templating approach is to generate a semi-crystalline (orcrystalline) morphology in the polymer coating. As crystals begin togrow, the surface spontaneously develops topology/roughness thatprecludes microbial adherence.

Scheme 2 below depicts a reaction according to embodiments of theinvention. A bis-trimethylsilyl protected dithiol (A) is combined withhexafluorobenzene and an organocatalyst to form the polymer (B). Polymer(B) is a highly hydrophobic, semicrystalline material that preventsbacterial adhesion and formation of biofilms.

According to an exemplary embodiment,2,2,11,11-tetramethyl-3,10-dithia-2,11-disiladodecane (A) is combinedwith hexafluorobenzene and triazabicyclodecene (TBD) or1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) to form a fluorinated polyetherpolymer (B).

The reaction and conditions shown in Scheme 2 exhibit very vastkinetics, with the reaction being complete in less than two minutes atroom temperature, a distinct advantage over current methods forpolythioether synthesis. Additionally, these reaction conditions allowfor the incorporation of commercially available perfluoroarenes,enabling access to a diverse array of new fluoropolymers. Incorporatingperfluoroarenes enables development of new, highly hydrophobic filmsbecause higher fluorine content confers increased hydrophobicity in theresultant material.

According to embodiments, a fluorinated polythioether is formed by anucleophilic substitution reaction including a perfluoroarene, adithiol, and an organic catalyst.

After the films are cured, contact angles with water are increased.After the films are cured, contact angles with water greater than 90°are achieved in some embodiments. After films are cured, contact angleswith water greater than 95° are achieved in some embodiments. Afterfilms are cured, contact angles with water greater than 99° are achievedin some embodiments. These results demonstrate the efficacy of thepolymer forming reaction for accessing new fluorinated materials andtheir use in hydrophobic coatings. Given the general effectiveness ofthese conditions for a wide variety of activated fluoroarenes andsilyated thiol nucleophiles, this can allow for the rapid development ofa broad range of new hydrophobic materials.

The fluorinated polythioethers are semi-crystalline (or crystalline) andopaque with a glass transition temperature (T_(g)) of about 24° C. and amelting point (T_(m)) of about 102° C. in some embodiments. In otherembodiments, the fluorinated polthioethers are semi-crystalline (orcrystalline) with a glass transition temperature (T_(g)) in a range ofabout 50 to about 200° C., and a melting point (T_(m)) in a range ofabout 0 to about 350° C.

According to one or more embodiments, a method of making an antifoulingand bactericidal coating with tailorable surface includes depositing alayer of branched polyethyleneimine (BPEI) and diamino-functionalizedpoly(propylene oxide) (PPO) in an organic solvent on a substrate to forma layer of BPEI/PPO. The method includes depositing a layer of glyoxalin a water-containing solution on the layer of BPEI/PPO. The methodfurther includes curing the layer of BPEI/PPO and layer of glyoxal toform a homogenous, glyoxal crosslinked BPEI/PPO coating. The curinginduces local precipitation and alteration of a surface topology of theglyoxal crosslinked BPEI/PPO coating to provide a textured surface.

Curing the layer of BPEI/PPO and layer of glyoxal to form a homogenous,glyoxal crosslinked BPEI/PPO coating provides advantages of a coatingwith positively charged ammonium ions that are bactericidal.

Curing to induce local precipitation and alter a surface topology of theglyoxal crosslinked BPEI/PPO coating to provide a textured surfaceprovides advantages of providing an irregular surface so that bacteriacannot attach.

According to one or more embodiments, a method of making an antifoulingcoating with tailorable surface topology includes providing a mold witha pattern of indentions and protrusions. The method further includesforming a layer of fluorinated polythioaminal on the pattern ofindentions and protrusions of the mold. The method includes heating thelayer of fluorinated polythioaminal to induce crosslinking and transferthe pattern into the layer of fluorinated polythioaminal. The methodfurther includes removing the mold from the layer of fluorinatedpolythioaminal, the layer of fluorinated polythioaminal including anegative pattern of the mold.

Forming a layer of fluorinated polythioaminal on the pattern ofindentions and protrusions of the mold and then heating the layer offluorinated polythioaminal to induce crosslinking and transfer thepattern into the layer of fluorinated polythioaminal provides advantagesof a textured surface that inhibits microbial adhesion and subsequentfouling.

According to one or more embodiments, a method of making an antifoulingcoating with a textured surface includes forming a fluorinatedpolythioether by a nucleophilic aromatic substitution reaction, andcuring the polythioether to provide a film that is semi-crystalline orcrystalline.

Forming a fluorinated polythioether by a nucleophilic aromaticsubstitution reaction occurs with very fast kinetics at roomtemperature, which allows incorporation of a wide array ofperfluoroarenes.

EXAMPLES Example 1

A textured surface was formed on a substrate. A solutions of PEI anddiamino-functionalized poly(propylene oxide) (PPO) in isopropanol and asolution of glyoxal in a mixture of isopropanol and water weresuccessively deposited onto a substrate and then cured. Phase-separationof the network occurred during curing due to the PPO being present insolution. Without being bound by theory, phase-separation likelyoccurred due to the progressive evaporation of the isopropanol solventand immiscibility of PPO in the remaining water solvent.

FIG. 3 depicts the profilometer trace of the coating (film), whichillustrates the surface's profile to quantify roughness. As shown,phase-separation resulted in a rough micro-patterned surface.

Example 2

The antifouling properties of nano-patterned PEI/PPO/glyoxal coatingsand control non-nano-patterned PEI/glyoxal coatings were tested. Eachcoating was incubated for 24 hours with Staphylococcus aureus (SA) andPseudomonas aeruginosa (PA). Metabolic activity of SA after beingincubated with each coating is shown in FIG. 4A. Metabolic activity ofPA with each coating is shown in FIG. 4B. Live/dead assays against SA(top) and PA (bottom) are shown in FIG. 4C.

All the tested coatings exhibited very good antifouling properties forboth SA and PA, as compared to a control glass substrate. However,coating 526 (nano-patterned) demonstrated significantly better resultsas compared to the other non-nano-patterned coatings, including 524, 527and 528, which were chemically-modified to induce chemical bacteriarepulsion.

Glass substrates for these experiments were prepared as follows. 3inch×2 inch glass slides were dipped in a surfactant solution overnight,rinsed with water and ethanol and dried. The slides were next treated byultraviolet (UV)/ozone for 15 minutes. Clean slides were dipped in a 10%APTES solution in ethanol for 30 minutes and thoroughly rinsed withethanol before drying. Aluminum tape (80 micrometer thickness)boundaries were next installed, and the slides were kept under nitrogenbefore spray coating.

PEI/PPO/glyoxal films were prepared by spray-coating as follows.Solution A was 2.5 wt % glyoxal solution in isopropanol/water. SolutionA was prepared by diluting a 40 wt % aqueous solution with isopropanoland then transferring into a 22 milliliter-reservoir of a spray gun.Solution B was 0.563 grams PEI (M_(w)=1.8k) and 0.225 grams JEFFAMINED-4000 Polyetheramine D4000 (Huntsman Corporation, The Woodlands, Tex.)in 14 grams isopropanol. Solution B was transferred to the 22milliter-reservoir of a second spray gun. The layers were sprayedsuccessively on an APTES-functionalized glass substrate. The distancebetween the substrate and the nozzle was about 15 centimeters. SolutionA was first applied, followed by solution B, until a total of 9 layerswas reached (pressure=25 psi). The glass substrate was then transferredto a hot plate to cure. The following thermal treatments were used forcuring: 30° C. for 1 hour, 30° C. to 120° C. for 1 hour, and 120° C. for1 hour. The film was cooled to room temperature after curing.

Example 3

A hydrophobic polythioaminal was prepared.4,4′-hexafluoroisopropylidene)dianiline and 1,6-hexanedithiol werereacted in equimolar ratios with an excess of paraformaldehyde (2.5equivalents) at 85° C. After 18 hours, a polymeric material was formed,which resulted from the in-situ generation of a reactive imineintermediate that condensed with dithiol to form the polythioaminal (seereaction scheme in FIG. 5A).

FIG. 5B depicts a gel permeation chromatography (GPC) trace of thepolymer that was formed. The polymer had a M_(w) of 19,238 g mol⁻¹, aM_(n) of 10, 689 g mol⁻¹, and a polydispersity index (PDI) of 1.80.

Example 4

A fluorinated polythioaminal (shown in FIG. 6C) was spin-coated onto thesurface of a substrate to form a linear polymer with a PDI of about 2.The polymer was heated to 110° C. to induce crosslinking and networkformation (also as shown in FIG. 6C). The contact angle of thecrosslinked, highly fluorinated polythioaminal network was thenmeasured, as shown in FIG. 7. The contact angle without optimization ofthe network at 108° is shown. The roughness of the coating afterspin-coating was not modified.

Example 5

A fluorinated polythioether was prepared as follows. A 8-mLscintillation vial equipped with a magnetic stir-bar was charged with2,2,11,11-tetramethyl-3,10-dithia-2,11-disiladodecane (A in Scheme 2above) (281 mg, 1.0 mmol) and dimethylformamide (DMF) (1.0 mL).Hexafluorobenzene was added, followed by TBD (14 mg, 10 mol %). Within 2minutes, a white solid had precipitated from solution. Methanol (7 mL)was added to the reaction mixture, and the solid was collected bycentrifugation and decanting the supernatant. This process was repeatedtwo additional times to afford the desired polythioether polymer (B inScheme 2) as a white solid.

The product was characterized as follows: M_(n,SEC)=20,200 g/mol,M_(w,SEC)=90,600 g/mol; DÐ=4.5. ¹H NMR (400 MHz, CDCl₃)=ä2.92 (m, 4H),1.56 (m, 4H), 1.41 (m, 4H).

Dynamic Mechanical Analysis (DMA) was performed. AnN-methyl-2-pyrrolidone (NMP) solution of the fluorinated polythioetherwas prepared and drop-casted on a braid for DMA analysis. The samples(approximately 12×6×1 mm) were solicited using a dual cantilever withthe following temperature program: (1) heating from −80° C. to 220° C.at a 5° C./minute heating rate, (2) cooling from 220° C. to -80° C., and(3) heating from −80° C. to 300° C. Alternatively, the polymerization ofthe fluorinated thioether material was performed on the braid andobtained material exhibited similar DMA traces.

FIG. 8 depicts the DMA results, which is a graph of storage modulus as afunction of temperature for the fluorinated polythioether. As shown, thefluorinated polythioethers are semi-crystalline, demonstrating therequisite surface roughness and was opaqueness due to the sphericalcrystal structure.

Various embodiments of the present invention are described herein withreference to the related drawings. Alternative embodiments can bedevised without departing from the scope of this invention. Althoughvarious connections and positional relationships (e.g., over, below,adjacent, etc.) are set forth between elements in the followingdescription and in the drawings, persons skilled in the art willrecognize that many of the positional relationships described herein areorientation-independent when the described functionality is maintainedeven though the orientation is changed. These connections and/orpositional relationships, unless specified otherwise, can be direct orindirect, and the present invention is not intended to be limiting inthis respect. Accordingly, a coupling of entities can refer to either adirect or an indirect coupling, and a positional relationship betweenentities can be a direct or indirect positional relationship. As anexample of an indirect positional relationship, references in thepresent description to forming layer “A” over layer “B” includesituations in which one or more intermediate layers (e.g., layer “C”) isbetween layer “A” and layer “B” as long as the relevant characteristicsand functionalities of layer “A” and layer “B” are not substantiallychanged by the intermediate layer(s).

The following definitions and abbreviations are to be used for theinterpretation of the claims and the specification. As used herein, theterms “comprises,” “comprising,” “includes,” “including,” “has,”“having,” “contains” or “containing,” or any other variation thereof,are intended to cover a non-exclusive inclusion. For example, acomposition, a mixture, process, method, article, or apparatus thatcomprises a list of elements is not necessarily limited to only thoseelements but can include other elements not expressly listed or inherentto such composition, mixture, process, method, article, or apparatus.

Additionally, the term “exemplary” is used herein to mean “serving as anexample, instance or illustration.” Any embodiment or design describedherein as “exemplary” is not necessarily to be construed as preferred oradvantageous over other embodiments or designs. The terms “at least one”and “one or more” are understood to include any integer number greaterthan or equal to one, i.e. one, two, three, four, etc. The terms “aplurality” are understood to include any integer number greater than orequal to two, i.e. two, three, four, five, etc. The term “connection”can include an indirect “connection” and a direct “connection.”

References in the specification to “one embodiment,” “an embodiment,”“an example embodiment,” etc., indicate that the embodiment describedcan include a particular feature, structure, or characteristic, butevery embodiment may or may not include the particular feature,structure, or characteristic. Moreover, such phrases are not necessarilyreferring to the same embodiment. Further, when a particular feature,structure, or characteristic is described in connection with anembodiment, it is submitted that it is within the knowledge of oneskilled in the art to affect such feature, structure, or characteristicin connection with other embodiments whether or not explicitlydescribed.

For purposes of the description hereinafter, the terms “upper,” “lower,”“right,” “left,” “vertical,” “horizontal,” “top,” “bottom,” andderivatives thereof shall relate to the described structures andmethods, as oriented in the drawing figures. The terms “overlying,”“atop,” “on top,” “positioned on” or “positioned atop” mean that a firstelement, such as a first structure, is present on a second element, suchas a second structure, wherein intervening elements such as an interfacestructure can be present between the first element and the secondelement. The term “direct contact” means that a first element, such as afirst structure, and a second element, such as a second structure, areconnected without any intermediary conducting, insulating orsemiconductor layers at the interface of the two elements.

The terms “about,” “substantially,” “approximately,” and variationsthereof, are intended to include the degree of error associated withmeasurement of the particular quantity based upon the equipmentavailable at the time of filing the application. For example, “about”can include a range of ±8% or 5%, or 2% of a given value.

The descriptions of the various embodiments of the present inventionhave been presented for purposes of illustration, but are not intendedto be exhaustive or limited to the embodiments disclosed. Manymodifications and variations will be apparent to those of ordinary skillin the art without departing from the scope and spirit of the describedembodiments. The terminology used herein was chosen to best explain theprinciples of the embodiments, the practical application or technicalimprovement over technologies found in the marketplace, or to enableothers of ordinary skill in the art to understand the embodimentsdescribed herein.

What is claimed is:
 1. A method of making an antifouling andbactericidal coating with tailorable surface topology, the methodcomprising: depositing a layer of branched polyethyleneimine (BPEI) anddiamino-functionalized poly(propylene oxide) (PPO) in a mixture of waterand organic solvent on a substrate to form a layer of BPEI/PPO;depositing a layer of glyoxal in a water-containing solution on thelayer of BPEI/PPO; and curing the layer of BPEI/PPO and layer of glyoxalto form a homogenous, glyoxal crosslinked BPEI/PPO coating; where thecuring induces local precipitation and alteration of a surface topologyof the glyoxal crosslinked BPEI/PPO coating to provide a texturedsurface.
 2. The method of claim 1, where the organic solvent isisopropanol.
 3. The method of claim 1, where the water-containingsolution is a mixture of isopropanol and water.
 4. The method of claim1, where the homogenous, glyoxal crosslinked BPEI/PPO coating includespositively charged quaternary amines that provide bactericidalproperties.
 5. The method of claim 1, further comprising functionalizingthe substrate with NH₂ moieties before forming the layer of BPEI/PPO. 6.The method of claim 1, where the textured surface exhibits alteredsurface topology on the nanoscale or the microscale.
 7. The method ofclaim 1 further comprising depositing one or more additional layers ofBPEI/PPO and one or more layers of glyoxal before curing.
 8. The methodof claim 1, wherein depositing the layer of BPEI/PPO and the layer ofglyoxal is by spray-coating.
 9. A method of making an antifoulingcoating with tailorable surface topology, the method comprising:providing a mold with a pattern of indentions and protrusions; forming alayer of fluorinated polythioaminal on the pattern of indentions andprotrusions of the mold; heating the layer of fluorinated polythioaminalto induce crosslinking and transfer the pattern into the layer offluorinated polythioaminal; and removing the mold from the layer offluorinated polythioaminal, the layer of fluorinated polythioaminalcomprising a negative pattern of the mold.
 10. The method of claim 9,wherein the layer of fluorinated polythioaminal is linear beforeheating.
 11. The method of claim 9, wherein a polydispersity index (PDI)of the fluorinated polythioaminal before heating is about
 2. 12. Themethod of claim 9, wherein forming the layer of fluorinatedpolythioaminal is by spin-coating.
 13. The method of claim 9 furthercomprising forming the fluorinated polythioaminal by reacting afluorinated dianiline and dithiol with paraformaldehyde.
 14. The methodof claim 13, wherein reacting the fluorinated dianiline and dithiol withparaformaldehyde in-situ forms an intermediate imine that reacts withthe dithiol.
 15. A method of making an antifouling coating with atextured surface, the method comprising: forming a fluorinatedpolythioether by a nucleophilic aromatic substitution reaction; andcuring the fluorinated polythioether to provide a film that issemi-crystalline or crystalline.
 16. The method of claim 15, wherein thenucleophilic substitution reaction comprises a perfluoroarene reactant.17. The method of claim 16, wherein the nucleophilic substitutionreaction further comprises a dithiol.
 18. The method of claim 17, wherethe nucleophilic substitution reaction further comprises an organiccatalyst.
 19. The method of claim 18, wherein the organic catalyst istriazabicyclodecene (TBD) or 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU).20. The method of claim 15, where the film is opaque.